Precigen, Inc. (PGEN) Earnings Call Transcript & Summary

And precision value and health have been advancing clinical and drug development, manufacturing and commercialization for the regenerative medicine sector for the past 10 years. Having been a partner to over advanced therapy organizations, we understand the complexities to bring a cell and gene therapy to market. Since our last day at the union addressed that advanced therapy landscape has changed significantly. During today's panel, we will be hearing from various experts on their respective companies. their perspectives on some of the roadblocks and opportunities in the cell and gene therapy development and the future of the sector moving forward. Now I'll briefly introduce our panelists. Joining us today are Dan Kirby, Chief Commercial Officer, Orca Bio. Welcome, Dan. Deborah Phippard, Chief Scientific Officer at Precision for Medicine. Helen Sabzevari, President and CEO of Precigen. Devyn Smith, CEO of Arbor Bio and Chad Salisbury, Senior Vice President of Project Pharma. All right. Let's get this rolling. To start, I would love to hear from each one of our panelists on their respective companies, the progress that you've made this year and your plans moving forward.

Dan, starting with you. Can you tell us a little bit more about Orca Bio and Orca's high-precision cell therapies can build a new healthy blood and immune system for patients?

Thank you, Anshul, and thank you, [ indiscernible ] for having me. Orca Bio for those who aren't familiar, is a late-stage cell therapy company based out of the Bay Area. We spun out of Stanford in 2016. And our focus is to replace disease immune systems from patients with inside of patients with healthy ones from donors. Our cell therapies are starting in the HemOnc space. Our lead asset, Orca-T, is in a Phase III randomized trial comparing to a standard allograft in ALL, AML and MDS with the goal of improving chronic GvHD free or graft versus host free survival in patients. We're starting in the HemOnc space, as I mentioned. We also have another asset, Orca-Q, which is looking at initially haplo donors, so a different donor mix. of replacing immune systems with a related donor, but we also are expanding into a nonmalignant space and then eventually into autoimmune with our company. We have 2 presentations at ASH next month, one on Orca-T and one on Orca-Q if you want to learn more about our data.

That's awesome, Dan. Thank you so much. Helen, moving on to you, can you give us some insight on your customer innovative platforms and how they are helping to pioneer the next generation of precision immunology through novel multifunctional gene cell therapies.

Yes, absolutely. Precigen is a cell and gene therapy company that we started in actually January 2020. And it mainly focuses on editing either the immune system from outside by taking the cells and developing an UltraCar which are specific T-cells against both hematological and solid tumors. But with the caveat and differentiation of an overnight manufacturing way to win is absolutely it's 24 hours, and this can be done at the hospital, so you do not need a centralized manufacturing facilities which addresses now with the editings that has been done in genetic modification of the autologous T-cells of the patient themselves within 24 hours in a nonviral fashion at the hospital, we can infuse these cells back to the tumors. They have the ability to persist and expand. And basically, you are manufacturing directly within patients which leads to much lower cost, time to the patient is much faster. At the same token, we have another platform that -- what it does, it addresses the basically education of immune system from within is our gorilla AdenoVerse platform, which we are very excited in August. We have a number of programs in that as well. We have to 3 major program on UltraCAR in hematological space, AML, ALL, CLL as well as the solid tumors ovarian cancer and triple-negative breast cancer. On our AdenoVerse platform, we have been -- we have our PRGN-2012, which received an accelerated path from the FDA this summer and we are looking to submission of the BLA in a recurrent respiratory papillomatosis, which is a rare disease of the patients that there has been no treatment prior before. and also the AdenoVerse platform, which uses the gorilla vectors to educate the immune system via vaccination. For HPV cancers, especially in cervical cancer as well as in head and neck. So we are very excited about that.

Thanks, Helen. And congratulations on all the success. Debs, earlier you gave a brief introduction to precision for medicine. Can you tell us a little bit more about precision and how it's working with advanced innovators to develop therapies for patients?

Yes. Thank you, Anshul. I'm sure everybody in this audience knows that developing cell and gene therapy for patients is complicated, really takes a diverse complex team, and that's what Precision and our precision advanced collective really does. So we can help with all aspects of getting cell and gene therapy to a patient, everything from working with you about manufacture of drug, cold chain logistics, drug supply, getting those drugs on site. Working on the clinical trial protocols, helping with the INDs, lab assays. We want to know is the therapy doing something? Is it on target, have we got safety efficacy assays, all the way through to market access how are you going to launch that drug? What should it be priced at? Clients come to us, some want everything help in every one of those areas. Others know that they have one particular need, and we're happy to help however we can. It's all about getting those drugs to the patients as rapidly as we can, Anshul.

Devyn, moving to you, can you tell us a little bit more about Arbor and its gene editing technology platform and the impact it will have to patients in the future?

Yes, absolutely. Thank you for having us here. So Arbor is a next-generation gene editing company. We were co-founded by Feng Zhang, who is the CRISPR pioneer out of the [ indiscernible ] MIT and David Walt, who is a high throughput automation expert cofounded Illumina. And the company was actually cofounded on an idea rather than IP. So all the IP is wholly owned internally. And that idea was Evolution has probably created a vast array of different approaches to thinking about editing. Let's build the capability to go out and really harness all that extensive work that evolution has done to turn those things into therapeutics. So we have over the last 5 to 6 years built a robust toolbox of editing approaches that we feel allows us to really -- rather than approach diseases with a single tool, we actually approach the disease first, understand what the disease needs from an editing perspective and then bring to bear the right tool and screen across our toolbox to identify that. Now we have -- our programs are really focused in the CNS and liver space in vivo. We do have partnerships in the ex vivo space, but we are not developing our own cell therapies. We're very focused on in vivo approaches. We do have a goal as a company of 3 filings over the next 3 years, with our first being in a liver indication in the second half of next year. And we view that the editing spaces. The key is it's a new modality. So let's treat it like a new modality and build the right tools that allow you to really tackle it as you would if you had a small molecule platform or an antibody platform where you need a broad toolbox of approaches and that's how we think about it. With the end goal being, as you said, on delivering these novel one-and-done approaches to patients that can hopefully revolutionize the way we think about health care over the coming decades and centuries.

That's amazing, Devyn. Thank you for giving us a little bit more insight into Arbor. I would love to turn our attention into new technologies. Obviously, there were a great deal of new -- great deal of approvals this year in the cell gene therapy space more than they have been in the past few years. And this space is always extremely innovative and extremely exciting. So I would love to get your perspective on new innovative technologies that are going to be -- that are creating -- they created all kinds of buzz this year and are poised for growth in 2024. So I'd love to ask a question to a panel. What would you say are some of your top technologies that are poised to break through in 2024. Helen, I would love to start with you.

Thank you. Well, from our perspective, I think it's -- really, we should address, first of all, we believe that cell and gene therapy is the next cutting edge in the field. as we have observed what has happened to the immunotherapies and immuno-oncology with the checkpoint inhibitor really this decade and the upcoming decades is the decades of precision medicine and of cell and gene therapy. In that space, what I really believe it's going to be unique and especially from our perspective, for us is the differentiation of the platform that, first of all, how do you modify the cells, especially the autologous T-cells which then you do not have to deal with a lot of the complication that is associated with the off-the-shelf and other therapies. But more importantly, how do you modify these cells in such a way that you do not need to manufacture in very, very large amount that leads to, first of all time that you lose time to get to the patient, but also from a perspective of the cost that, as we have seen with the cost of some of the very effective for instance, CAR-T therapies are, but it's not really -- cannot be sustained, especially if you move to the -- towards the repeat dosing or combination. So from our perspective, addressing, first of all, generation of autologous T-cells of the patients that can both go towards hematological and solid tumors with a very short manufacturing, which, in our case, our technology addresses in 24 hours and the release and infusion of the cell within that 24 hours. We believe that this is paradigm shifting as far as precision medicine is concerned. And as what it can be offered not only from addressing the cells that are not exhausted and putting it back to their patients, their own cells, but they can actually expand and react to their environment accordingly to what they see and there are safety mechanism associated with them that you can control. This is what we know that regulatory bodies have been asking for many years. And I think this is -- we are at the cusp of approaching that from precision. And also finally, from combining that with educating the immune system to see the tumor cells as enemies and development of our AdenoVerse platform, for instance, which has addressed some of the major limitation of other viral vectors and vaccines, which is basically you give it once and you have a neutralizing antibody. In this case, we have developed a platform that you can give a number of times. And as we have shown the data now that you can go upwards of 1.5 years of injection and you keep getting the enhancement of the T-cell. Having these platforms that are unique, differentiated and addresses not only the unmet needs of the patient, but also the manufacturing limitations that the field is seeing and the price stack bringing it down. So it's applicable for every patient. I think this is what is unique and paradigm changing for us.

I agree with you, that I think cost and redosing patients is certainly issues that the field has been facing for quite some time. Dan, what are some of the technologies that you're most excited about next year?

I think looking at it, the technologies where we've gone from autologous, antigen-focused CAR-Ts into gene editing and then evolution of the space from both cell and gene into looking at allogeneic approaches. And one of the things that our company is focused on because we are one-to-one allogeneic donor to patient is getting ourselves away from focusing on a CD19 or BCMA antigen to be able to affect the patient and not taking -- I love Helen's point about taking cells that are from a patient that could be tired and then challenging them. Our approach it's a bit different. We take cells from a healthy donor usually a younger, healthier donor. I think about having your immune system from when you were 20 years old. I think we all would love that for many reasons and love to see what that would do. But really looking at that approach of going into allogeneic, whether it be our approach or 1:1 where we're taking a diseased immune system and replacing it with a fresh one. That doesn't have the weaknesses that the current immune system has or even other allogeneic approaches where they're going off the shelf where they can have 10, 15, 20 products produced from one apheresis from a donor. That's very exciting in the space. And I think that's going to help bring us forward of expanding the current base with allogeneic in -- sorry, autologous into allogeneic.

Dan, Helen, I think -- I agree with both of you. I think both of you are trying to solve complex supply chain issues with your technologies that we've had in the cell therapy space for quite some time. And again, then with allogeneic cost again is on top of mind. And again, I would decrease the cost of these incredible medicines to patients. Deb, I think in your role, you see -- you work with a vast number of clients on the vast different types of companies. What are you seeing out in the field that you're really excited about?

Yes. Such a dynamic field, it's hard to really pick one thing. I think something that intrigues me is using AI for AAV capsid design. I find it sort of fascinating to think about getting accelerated ways. The goldilocks approach, if you like. We want better tropism. We work more durable expression. If we could get better safety, that's always a good thing. How do we think about that? I think really expands the toolboxes and let us have a lot more AAVs to be able to deliver our therapy. I think AAV has been demonstrated as a really good method to get gene therapy into patients. I always think about the flip side of that because I love the idea of having more specific capsids, better tropism to where we want to go. However, regulatory agencies are very concerned at the moment about preexisting immunity and are asking for those assays to be designed and run at a very high regulatory standard under IDE in most cases, Precision is very heavily involved in that. It's time consuming. It's expensive. I'm sure the entire industry would love to have one set of assays that will be applicable to the AAVs that are being used. So I'm very conflicted between biologically, I would love to have more targeted vectors on the immunogenicity side, that's a nightmare because we need a specific assay for every capsid and every disease state. We all know there's time and money costs around that. I think that whole field is going to evolve. So I guess I'm very excited to think about that. And then, of course, there's the whole gene therapy in neonates assuming we're going to have to redose those patients at some point how does that affect the whole AAV field, new vectors we're going to need, new ways of thinking about how to modulate the immune system. I think we're all going to be busy until retirement guys.

Yes. I think the AI space is fascinating, especially what it can do for the biotech field recently, my 12-year-old nephew just showed me how to use chat GPT on his phone and all of the different features that it has. So I'm really excited about how the applications of AI in biotech. Chad, in terms of -- you're on the forefront of manufacturing. Are there technologies on the manufacturing end that you see that are going to help us bring that cost down for cell gene therapies that you're excited about in the future?

I think a lot of the -- as we move more towards advances in single-use technology. I mean, there's been so much investment in the upstream process, but now you're starting to see technological breakthroughs in the downstream, which allow for better economics, but also a lot of the other suppliers are coming up with more innovative and higher-growth promoting medians that are tailored around the AAV space. So getting -- having higher cell densities, I mean better transfection. There's a lot of innovation in the plasma space in terms of are we going beyond the triple transfection process to more streamlined transfection, which will increase VG's per ML in the process. And then also in the days where we thought we might have to be going to 500-liter, 1,000-liter bioreactor, some of these disease states, we may be able to satisfy patient populations economically at smaller scales and have -- not have to continue to scale up and characterize those processes due to comparability between those different scales. So you reduce a lot of the work to be able to have an efficient, reliable, consistent process that is generating quality medicine.

Thanks, Chad. Devyn, last but not least, I would love your thoughts on what technologies do you think are poised to break through next year.

Yes. So I'll put on my alliance for General Medicine [ armature ]. I'm the Chairman of the Cell andgene therapy Industry Group. And if you look and what the space has accomplished over the last decade is amazing. A decade ago, there were very few things in the clinic let alone commercialize. This year, I think we'll have at least 5 approved new therapies. We may have our first approved gene editing therapy which is really amazing. And so I think we've moved from a space that was always kind of a theoretical. There's a lot of potential benefit to now you're actually seeing meaningful benefits to patients. And I think that is really exciting to -- like you take the CRISPR-Cas9 example and in just over a decade, we have -- we may have an approved therapy. And so I think it's exciting from that perspective. I think as we look across the cell therapy space, I think we've highlighted a few of the things here, it continues to move beyond sort of the liquid tumor space into the solid tumor space, moving from autologous to allogeneic, gene therapy moving beyond sort of the orphan diseases into new areas of delivery. I mean it's a fantastic time, I think, to be part of this industry and see all of this. Against the backdrop, there are some serious headwinds, I think, for biotech in general right now. But I do think on the -- on the size of benefits to patients and society, there's amazing amount of progress. And I think next year, we'll see again many more approved therapies and many more novel things entering the clinic that are technologies that you could only dream of 20 years ago.

That's a wonderful breakdown, and I completely agree with you, we just need to continuously need more approvals to continue to move the space forward. And I think this is going to be a banner year to do that in such a tough funding environment that we're in. I hear so many different things about gene editing. There's CRISPR-Cas9, there's base editing, there's prime editing. And they're all making their own impact in the industry. Is there one of those technologies that you're most excited about or one that's leading the way? Or do they all have their place in the industry, Devyn and Helen, would love your thoughts there?

I think -- so my take is if you look at the genetic diseases that exist today, you've got some diseases where you have too much of something so you want to knock a protein down. You've got other diseases where you want to rewrite sections where you may have some mutations to fix, and you could use a base added approach or a reverse transcriptase based approach. You have other disease where you have these large repeats by [ indiscernible ] or something where you need to remove that repeat region. And then you have other diseases where there are just so many mutations along that there maybe 5,000 patients, maybe 5,000 different mutational sites, where we actually just need to repair the entire gene and drop something in. And so I think if those are kind of the 4 basic things you want to do to really provide therapies from genetic diseases, I think there's different places where each technology has value. And so Arbor's view is, well, let's build a platform that allows you to tackle anything along that spectrum. And then you just have to pull the right tools and screen against it to identify the best way to do it. So I think -- there's -- I think there's room for a lot of different approaches here because there's a lot of different types of genetic diseases. Not to mention the use of editing as Helen and other companies are doing on the -- in cell therapy.

Helen, what are your thoughts?

No, I fully agree with Devyn. I think where we are depending on -- and this is the beauty of precision medicine, right? finally, we are getting there to define this term in a correct pattern because as Devyn said, there are diseases that there is a mutational change. And what you need to do is really edit specifically, either correct that or take out that mutation. And this with some of the technology that is out there now is very doable, and we are seeing the results of that. On the other hand, there are indications, as we see it in some of the rare diseases and also in cancer that what you need to do is basically retrain the immune system. Now either from outside generating cells that are specifically they can recognize and understanding the mechanism why these cells to start with, they were not able to recognize the enemy from within, for instance, in the cancer setting, right? and how do you train them? Or modify them that now once you put back this army back to the body of the patient, all of a sudden, the flag goes up and they can recognize the enemy and which is one of the things that we are doing by modifying and processing this UltraCar that they target very specific basically antigens that is highly expressed on the tumors of the patients and being able to generate and give it very rapidly. On the other hand, as Devyn mentioned, also, there are these scenarios that's really from within, meaning inside the patient body, you need to start generating for the lack of better word, a whole new group of soldiers and armies in your immune system to start from within and be very specific, the training is very, very specific. And going back to what Deborah was mentioning, I think the challenge is -- how do you come up with the viral vectors, with the vectors that they can repeatedly you can use and that is a one silver bullet at the time. And this is exactly one of the things that we found ourselves with our Gorilla platform addressing exactly what Deborah was mentioning that now come up with the new vectors and viral vectors that they can -- first of all, they have a much higher capacity so they can address much more genes to basically have the input for these viral vectors -- and then secondly, to continuously use them without production of neutralizing antibodies, which limits the neurotherapy and being able to continuously enhance the immune system with a very, very sort of good safety reason. And I think this is why this field right now is so exciting because all of these are at play for us to come and make a perfect precise medicine for the patient, and that helps at the end of the day also to get away from the usage of therapies that we know it might not work on 80% of the patients. The cost that is associated with it and the toxicity that the patient has to endure even though they are not getting the benefit of the therapies.

Yes. cheap, fast and safe, Helen, could you get on that?

Debs, I saw you nodding quite a bit when Devyn and Helen were speaking. Did you have anything to add?

No. I mean I just think that's a fantastic summary. I see a lot of space in the field. I think it will get winnowed down probably to 3 or 4 platforms approaches. But yes, it's not going to be 1 platform. I think what we're trying to tackle with cell and gene therapy is just a far too vast array as Devyn so clearly laid out. So we're going to need a fairly big toolbox.

One thing I wanted to follow up on was one of Devyn's comments and this is a question for you, Dan. Devyn mentioned all the places cell therapy is going and how it's starting to spread its wings from starting -- where we started for autologous to allogeneic and from oncology to other disease areas such as immunology and neurology. Would love your thoughts on where you see the cell therapy field moving towards?

Absolutely. And one of the things to think about where we came from. So I was with Juno back in 2016 when we were launching out and working along with colleagues at [ Kite ] and Novartis about how we were going to start off in the oncology space. and we were going to start off with diffuse large T-cell and looking into expanding into myeloma, I likened the progression of gene and cell therapy, almost like traditional development in oncology, starting in the late lines and working your way up. And the late lines here are those patients that were terminally ill patients in HemOnc. As we look at where we started and what's been accomplished with cell therapy there, you can see the potential to spread our wings. The Bluebird and others have tackled non-malignant, and that's a huge step forward, and we're looking at therapies, even our platform, what that would apply to a nonmalignant space with it. But getting into Devyn had mentioned solid tumors even in the oncology space before we leave malignant. Solid tumors is something that there are a ton of therapies out there and the industry has come a long way and what can gene and cell do there. It's a phenomenal potential for all of our companies and our platforms. But getting outside the oncology space, again, into autoimmune, that is something that we aspire to do, and we're starting to test our platform out with that. But if you can think about how we're progressing in our therapies, these are onetime cures for diseases. We're starting with the terminal patients and getting into other patient types. And if you can take the technology and understand that we are just at the beginning of it, and as we advance in both cell and gene, what could we do with patients who have MSRA, other just diseases they have to live with, where they're not terminal necessarily, but they're living a life that could be improved. And that really is something that we're all working towards. I do think there's a lot of noise in the autoimmune space. the various companies are really starting to explore that and dive into it. It's kind of one of those hot topics with investors as well. We see our platform translating very well in there if you replace another person with autoimmune disease and replace their immune system, what's the potential there? They're doing some autologous work. With transplant there. We think our therapy has been proven to be better than that. So again, that is where these companies have so much potential, all of us to be able to affect only lives of patients who are terminally ill, but look at diseases where people are living a life that could be improved, and we could do that and add tremendous value into the system.

Helen, did you want to add anything to that comment as well?

Yes. No, I fully agree with that. And I think -- from the perspective of cell and gene therapy, I -- Dan is absolutely correct. I think we have just scratched the surface with the hematological, for instance, oncology and some of our like various therapies like CAR-Ts or TCRs and all of this, where I think, again, is different is to understand what we are going through right now with the cell and Gene therapy is exactly what I went through when I was doing immuno-oncology when it was not chic and in style many, many years ago. And that is the fact that, first, you have to understand the problem. Where is it that we are coming short, for instance, in solid tumors. And in a space of the cell therapy, for instance, one of the things that has been shown everyone talks about it as well, we are not trafficking. We are not getting ourselves there. The reality is that we are not addressing some of the basic mechanisms that are involved in inhibition of these cells of -- and persistence of these cells. The cells that we have, again, I will take it back to some of the basic stuff that we do with the manufacturing, even though we have a very potent cells if we do classical manufacturing, but you have generated the type of cells that -- they are at the end of their life. And by putting billions of them in there, they don't necessarily have a long time to get there. What we have to do is make a better cell therapies that they are younger, more active they can persist, they can expand, and they can stay around for a long period of time. So the therapy has time, especially in a view of a solid tumor that these cells do not see the enemy. They do not see the tumor cells immediately in the blood. They have to travel, and they have to get to these cells. And the context of the autoimmune I fully agree. I think what we are learning in oncology. It can quite be applicable into the autoimmunity with the caveat. And Dan said it, these patients are not terminal. These patients have a chronic disease that has to be treated. So the safety needs to be considered, how safe the treatment is. The second issue is the cost of these treatments. You cannot be looking at a patient cost that is Stage IV oncology versus a lupus patient, for instance. That has years to go through and then having a drug that is going to cost just as much, especially in the arena of the cell therapy, be it specific ones or the off-the-shelf that you can expand, it has -- again, it comes back to those fundamental issues of differentiation and changes that we have to make in order to manufacture faster, better, less money and get it to the patient as fast and all patients have accessibility and especially in a chronic disease because you are facing with the scenario of a treatment against steroids if you do not have a good basically base and cost effective and also safe treat.

Thanks, Helen. I'd love to shift our attention now to investor confidence in cell and gene therapy and the markets. Obviously, the markets have definitely influenced investor confidence in 2023, and that trend will continue on into 2024. These markets are severely impacting innovation. Chad, I would love to hear from you on how do you think the markets are affecting innovation and what that will look like moving forward.

Sure. I think just in the 35 minutes that we've been on this, the webinar, I think everybody that's listening should be very confident that there is significant innovation across the advanced medicine space and disease states that have evaded science are continuing to be challenged with this innovation and technology. So I think the innovation side is there. On the -- from a market perspective, and we do have to face reality, this stuff doesn't come for free and it is driving greater prioritization and focus within companies. Therapeutic innovators are having to reassess their pipelines and really redefine what that product runway is based on funding. So advancing I've seen some companies where it's like we're going to do 2 INDs a year. Well, maybe 1.5 years ago, maybe the funding was there, probably at this point. that's a pretty tall task. So you see maybe an IND a year, an IND every 18 months. because generating clinical data is absolutely critical for the success of the product but also for future raises so really prioritizing that pipeline is absolutely critical. And then that has had a knock-on effect on available manufacturing capacity that's out in the market, especially within the CDMO space. The cost of capacity, the time lines for securing that capacity have improved over the last year. A year ago, the costs were a lot different and the time to get that capacity was different. So I think that there are some opportunities out there. But again, it really gets back to prioritizing those pipelines and making sure that they're advancing the right candidate with the funding that they have.

Devyn, you and Helen, both Arbor and Precigen have weathered the storm and navigated exceptionally well from -- at least from what I could see. I would love to hear from you, Devyn, first on how have you weathered the storm? And what is your strategy going to be moving into next year?

Yes. It is an important question. I think -- as we look at the -- as Chad said, if you look at the markets, it's not just limited to cell and gene therapy. It's sort of biotech in general. I think it's taking lumps, but there are areas that are sort of doing better than others. And I think we're fortunate to be in gene editing, where I think there's a little where folks recognize the innovation and the potential that it has, looking ahead over the coming years. I think we also see a fair amount of good tailwinds by some of our peer companies like Intellia and others that are -- CRISPR. And so that, I think, helps us as well as others in the space. I think to your point on weathering. I mean I think it's about -- I think Chad nailed that, which is we have to always be focused on what we do well, what's our core piece and not deviate and try not to get caught up with shiny new objects that keep coming across our path. The scientists would love to do that, but focus on what's core, what we need to do and let's focus on execution. And then as I think, Chad said that clinical data will speak for itself. And that's ultimately what we want to do is get these things to patients. And so we spent too long chasing every perfect item, you'll never get to patients. So it's focus and execution, I think, for us.

Yes, I think that's right. I think focusing on innovation and proving out that innovation is critical. And I think that will lead to more funding to additional pipeline -- programs that you were able to develop through your pipeline. So I think that's very relevant. Helen, how have you weathered the storm? And what is 2024 going to look like for you?

Yes. No, definitely, I agree with everything that was said and highlighting that definitely has been tough years for biotech in general for everyone. And I think part of the issue that has been was a lot of capital was drawn at sort of platforms that were not well differentiated or they could not withstand the pressures of clinical data as well as scaling up and commercialization. And that's what we have seen that has been one of the issues with the undifferentiated platforms. I am a believer that this market, and we have been through this before, and we will get through it again, that innovation will survive. If you have a differentiated portfolio, that you can position it and get to the clinic rapidly and also design well, meaning both on research as well as the development and focus, and I agree with Devyn, not to go after shiny objects, differentiate from the beginning, extremely well your platform, tested that it's up in the par for scaling up and commercialization and then execute, execute with the plan Bs. I think and focus on your portfolio, eventually innovative platform, differentiated platform, they will show that data in the clinic. And that, for us, has been the case, for instance, in regard to both of our platforms that we're completely differentiated unique, but we have to get to the clinic to show the potential of this and as I mentioned, on our UltraCAR-T, it led to the -- achieving the fast track on AML from FDA and showing the data that we have shown at ASH but also on our AdenoVerse platform to the point the running our Phase I, Phase II, a single arm that had now as a result of the data of a 50% response rate in these patients in RRP, complete responses. The FDA has given us the breakthrough, but also the accelerated path for the BLA. And for us, 2024 is going to be a very exciting year because it's a year that Precigen company moves from being, of course, a company that started with the discovery and development towards the commercialization and the submission of the first BLA, and this is quite exciting. And I think that will, obviously, would be the jump start for all of the other programs that are coming, both in AdenoVerse and UltraCar platforms. which we are looking to finishing the Phase Ib and the discussions with the FDA about Phase II.

Thanks, Helen. Debs, continuing on to trends that we've seen this year and things are -- to look out for in the future. As a result of the markets, we've certainly seen a lot more consolidation and collaboration in the sector to help the delivery of life-changing therapies. Are there any challenges that you see as this collaboration happens between academic institutions, industry partners and sometimes even government agencies?

Yes, sure. Great question. we're all scientists. We probably fundamentally all agree. Collaboration is a fantastic idea. Doing that in reality has its own challenges. One change I've certainly seen in the last year is however, a collaboration is structured, I'm seeing more milestones, and I'm seeing money get parceled out in smaller and smaller increments. What that means for us on the clinical trial side is we are literally looking at data patient by patient. So you can imagine with a clinical study, we've got PK data, we've got PD data. We've got safety data. We typically want to run our assays batch, QC, QA data, deliver it, look at it with the Drug Safety Monitoring Board. Historically, we do that cohort by cohort in dose escalation. We are literally doing it patient by patient now. So that means a lot faster turn on assays, smaller batches, delivering the data, attempting to interpret data, but I see a lot more pressure. We've dosed a patient, show me that drug, was on target, show me I've got PK. I see the whole clinical trial space fundamentally shifting because of how those collaborations are getting negotiated.

Dev, I'm asking you to follow up on the -- I mean you're wearing your [ arm hat ], how do you see collaborations and consolidations moving forward.

Yes. I think one of the things I think historically in our space is everyone's looking for the big company partnership. That's sort of a big validation. And we've done -- we have several partnerships with Vertex that fit that bill. But I think importantly, beyond the big company partnership and working together, I think there's opportunities for smaller biotechs to work together. And I think beginning to realize that -- there are -- in our space, for example, there are companies that have unique capabilities and delivery to a particular tissue organ that we don't have. And is there a way to work together to put our differentiated payload with their delivery technology. These types of things, I think we'll start to see more of across, I think, the cell and gene space, because it's a way for all of us to get more bang for our buck, where we can partner with another company that's got different technology to bring things forward that at some point, maybe it's -- maybe we do partner with a big company on that particular program or we partner with somewhere else. But I think we've got to, I think, expand our view of what partnership looks like because there's a lot of really interesting technology in smaller companies that I think we have to begin to work together more and do more of that.

Thanks, Devyn. Dan, as we look towards 2024, certainly, the number of approvals that we've had this year is going to help the landscape. But how do you see the pricing and the reimbursement landscape evolving as more and more approvals come through at such a significant pace?

Great question, Anshul. And It's 45 minutes in, and we're talking about reimbursement, which is always an elephant in the room. Every time I run into an investor, everything in the sector. We have great science. We show that we can do it. We bring these things forward, but we still haven't had that huge win where we have a multibillion-dollar product or one that changes the game where investors say, "Hey, gene and cell, that is the future." We're going to go ahead and get very excited over other areas. And if you think about that, that's what happened to Biologics when they had their first wins, it really comes forward and it drives more investment in the space, more access for patients. If you can think about back in the early days with CAR-Ts, we were talking to CMS. I remember walking in there in December of 2016. And it was tough because we were a onetime administration of a therapy that the system wasn't used to and wasn't set for, specifically in the U.S. If you look at the U.S. landscape, we have public insurance, but also the commercial insurance is it varies by patient. And again, patients usually stay about 2 years on a plan, they switch from Aetna to Cigna. That's very hard for a onetime administration where you're taking 5, 10 years of very dense cost of the health care system and you're alleviating it all in the same year. So that's been a challenge. And when I do see the evolution happening, it started with CMS stepping up and creating DRG 018 for CAR-Ts and other immunotherapies. They also have [ CMMI ] looking and they're willing to engage with us about innovative ways of payment. They're looking at how we can get Medicaid by banning the states together and doing value-based deals. When you talk to the commercial payers, that same, let's figure out a way to do this, attitude has really evolved. So these 9 therapies coming through it is something that they'll get the benefit of the past, but they have to keep blazing the future. I mean we're in a Phase III trial. We're expecting to finish enrollment soon, the first part of next year. And then we'll have our data hopefully in 2024 and then move forward to filing. We've already had discussions. I was brought on to Orca based on my experience. And as we were working with the FDA designing our Phase III trial, I was talking to payers. And providers and physicians and patients into what's the feedback? What do you need to see to drive value? Because price is one thing, value is another. And looking at the value of these therapies, if you don't design your trials, which we have done with our primary endpoint and our secondary endpoints, you design your trial with the right endpoints to justify the reimbursement and that is the path forward. It's something that really hasn't been in the forefront. And I can tell you from being here for 3 years and helping design the trial into a toxicity and survival end point with tracking relapse, tracking hospitalizations, tracking everything, being able to go forward with the target product profile that's showing superiority in reducing toxicities improving survival, improving relapse really is something that as we're going and thinking about our pricing work, and I'm sure those 9 companies are doing the same thing, is that when you look at the endpoints you have it's very interesting as we engage with payers right now, they are pretty much telling us, if you hit this, and you can actually show these types of improvements now you're bringing value to us. Now we want to reimburse. And I think that is the first step that [ indiscernible ] of these companies, and we're all rooting for each other to succeed here. because we need a couple of really big wins here. But I do think it's on the onus of the manufacturer to engage early with the payers, the providers, the physicians and the patients to understand what's important when you come out of your trial to have the right endpoints and justify the right value because these things aren't cheap. But if you look at this in the span of taking multiple years of cost to the system, you can actually show that you're saving the health care system money, and that is something that the payers are very eager to do if you have the right inputs.

Thank you, Dan. In addition to, like Dan mentioned, I mean obviously, we need big wins. Are there other things that we can be doing as a sector to gain more momentum and to gain additional investor confidence as we head into 2024. Helen and Devyn, would love your thoughts here.

Absolutely. I think from my perspective, I go back to the point that we have, we need to -- as much as our preclinical data always looks wonderful and it's important, but what we need in order to gain confidence is to go back to a differentiated, innovative platforms that have the capability of being really scale up and ability to get to the clinic and show a clinical benefit for the patient. I think this is very important. Every single time that you have an innovative area, a cutting edge and in this case, cell and gene therapy and precision medicine what it bottom -- it come down. This is nothing new. We have seen this before, and it will happen again. once you show that you have benefit for these patients that you can be addressing 50, 60, 70, 80. And finally, my hope is 100% of the patients in the indication, and you're delivering benefit. I think this will bring the sort of confidence back. And as I mentioned, I think what we have gone through the past few years it has been very difficult. But in a way, now we are in a cleansing time for our industry as well, which separates the innovation, innovative platform, differentiated platforms and also platforms that they can lead to what Dan was mentioning that really justifiable treatments that patients can be using. And I think as soon as we start coming with those, and we have seen now some of them, we are getting approvals and as more of this happens, I think, obviously, we will become checkpoint inhibitors of the next decade. And I think that's where we are going and changing the parameters and paradigms.

Thanks, Helen. Devyn, final thoughts on what you think we can gain how -- what do you think you can do to gain additional momentum next year?

Yes. I mean, I always tell our team is there's things they can control and things we can on -- and the things we can't control the macroeconomic environment when interest rates start to come down, what happens on the global wars and all the other chaos that's going on. We can't control any of that. But we can control how well we execute, how we focus and bringing value to patients and to our shareholders through execution. And so that we're laser-focused next year, focus on bringing our first punitive product through to the clinic, making sure that we continue to execute across our other programs. And I think as an industry, as we all do that, focus, execute, it will get better, right? There's -- I think that you cannot continue as it is, right, for many more years or we have a very large problem, I think, in biotech in general. And so I think it's about making sure we continue to execute. It will get better on the external environment, and that will subsequently impact, I think, the overall economic environment for biotech. So I think focus on what we can control and then the things out of our control will hopefully resolve sooner than any of us hoped.

Thanks, Devyn. Well, we're almost out of time, and I know we can talk about the subject for many more hours. I'd like to ask the panelists one final question. What are you most excited about next year? Deb, starting with you?

I'm just blown away that we're finally getting these treatments through and getting them improved just seeing, I think, what, 8, 9 approvals that are in the pipeline, I mean, that's me. I mean, it's the combination of everything we do. So I'm just excited to see these patients get the therapies, the first gene editing, everything in the mainstream media about sickle cell. I can't believe how many of my non-scientist friends are asking me to explain that to them. This has really gone mainstream. I mean, I find that just super exciting and the thought that the big neurological diseases, Alzheimer's, Parkinson's, people are starting to think about maybe gene and cell therapies in those really intransigent spaces and not just fiction that we have a real shot not going to be next year, but things are definitely happening. So yes, I'm just excited that I agree with Helen. This is the IO space 10 years ago. So yes, I'm super excited to be working here.

Dan, what are you excited about?

I'm very excited next year that Orca Bio, we're going to finish out enrollment of our clinical trial. We're almost there right now. So we're hoping in the first part of 2024. We finish our enrollment. We're at time to end point. We have a great chance of having data in hand on our randomized trial. We treated 200 patients in single arm and the data looks phenomenal. So we're looking forward to that replicating in the pivotal trial and then moving forward with RMAT designation with the FDA and getting to the market. It's a really exciting time and something that 2024 is something we've circled years ago that this is the year where our data can come out. This is the year where we step forward and become a commercial stage company.

Thinking of getting to the market at Helen, I think I know what you're very excited about next year but let's hear it anyway.

Yes. No, absolutely. I'm going to echo -- first of all, I'm tremendously excited about the cell and gene therapy because I truly believe that this is the cutting it for the next decades to come. And in that view, I'm really excited about our platforms and our -- especially our PRGN-2012 program for RRP patients, these patients that they haven't had any treatment for the past 70 years. These are patients with developing the 9 tumors continuously. And the only thing is surgery. Some of the patients we have had they have required upwards of 300, 400 surgeries. Every 6 weeks, they require surgery. And having been able to show that with our basically platform and PRGN-2012,, we have 50% complete responders in patients moving now past 2 years post treatment and not requiring even a single surgery. This is really exciting. This is the power of the cell and gene therapy at its best. And for us, it's going to be an exciting year with pushing toward the BLA submission and commercialization for our organization with a view that -- of course, patients, the first thing, we are so excited about this. This is the first time, first therapy for patients in this space. using a cell and gene therapy. And then secondly, obviously, for our organization and our investors and really showing that a well-planned and executed plan can get there and have the confidence in the company. So.

Thanks, Helen. Chad, What are you excited about?

I'm going to take a little different twist. I think given the challenges that the industry has been through the last 12 to 18 months, I think all of us have had to re-think differently, like how do we design, how do we execute, how do we bring these products around what questions are really important versus which ones are interesting. And I'm excited to see as we come out of this are we stronger in terms of getting these products to patients. We have better knowledge, we have better decision-making and just seeing the overall health of the decision-making process in this industry, I think, is going to be something to see.

Devyn, final word?

Yes. I mean, from an Arbor perspective, we look forward to bringing our lead program towards the clinic next year. And then broader with an arm hat on the industry broadly, I just -- I'm really excited to continue to see all the progress we're making in helping patients. And then the other thing I would say is the FDA has done a fantastic job of being a good partner. And I think Peter Marks has done great and Nicole [indiscernible] and [ Hermie Bill ] is going to be a great partner, I think, to help us as an entry continue to make sure we deliver safe, effective treatments.

Thank you. Well, thank you, everyone, for participating. Truly an honor to be on panel with such esteemed folks for the cell and gene therapy industry, and thank you everyone out there for listening, and have a great day.